Cognitive Disorders One Year After COVID-19: Longitudinal Observations

Introduction

The COVID-19 pandemic has affected more than 418 million patients so far, and the number is increasing. The long-term impact of COVID-19 on cognition has become a major public health issue.

SARS-CoV-2 causes a variety of neurological sequelae in COVID-19 survivors, including dizziness, headache, myalgia, hypogeusia, hyposmia, polyneuropathy, myositis, cerebrovascular diseases, encephalitis, and encephalopathy. Such susceptibility of the central nervous system to SARS-CoV-2 has sparked great interest in neuropsychiatric research among COVID-19 survivors.

Cognitive complaints are common in the acute and subacute phases of COVID-19. Our research, along with that of others, has demonstrated an association between SARS-CoV-2 infection and cognitive performance in older adults months after infection. However, the long-term trajectory of cognitive changes after SARS-CoV-2 infection remains unknown. In this study, we investigated the 1-year dynamic trajectory of cognitive changes in older COVID-19 survivors.

Importance  

Determining the long-term impact of COVID-19 on cognition is important to inform immediate steps in COVID-19 research and health policy.

Aim  

To investigate the 1-year trajectory of cognitive changes in older COVID-19 survivors.

Design, environment and participants  

This cohort study recruited 3,233 COVID-19 survivors aged 60 years or older who were discharged from 3 designated COVID-19 hospitals in Wuhan, China, from February 10 to April 10, 2020.

Their uninfected spouses (N = 466) were recruited as a control population. Participants with cognitive impairment prior to infection, a concomitant neurological disorder, or a family history of dementia were excluded, as were those with severe heart, liver, or kidney disease or any type of tumor.

Follow-up of cognitive functioning and impairment was performed at 6 and 12 months. A total of 1438 COVID-19 survivors and 438 control individuals were included in the final follow-up. COVID-19 was classified as severe or non-severe following American Thoracic Society guidelines.

Main results and measures  

The primary outcome was change in cognition 1 year after patient discharge. Cognitive changes during the first and second 6-month follow-up periods were assessed using the Informant Questionnaire on Cognitive Decline in the Elderly and the Telephone Interview on Cognitive Status, respectively.

Based on the cognitive changes observed during the 2 periods, the cognitive trajectories were classified into 4 categories:

1. Stable cognition.
2. Early onset cognitive impairment.
3. Late-onset cognitive impairment.
4. Progressive cognitive impairment.

Conditional and multinomial logistic regression models were used to identify factors associated with the risk of cognitive decline.

Results 

Among the 3,233 COVID-19 survivors and 1,317 uninfected spouses examined, 1,438 participants who were treated for COVID-19 (691 men [48.05%] and 747 women [51.95%]; median [IQR] age , 69 [66-74] years) and 438 uninfected control individuals (222 men [50.68%] and 216 women [49.32%]; median [IQR] age, 67 [66-74] years) completed the 12-month follow-up.

The incidence of cognitive impairment in survivors 12 months after discharge was 12.45%. Individuals with severe cases had lower scores on the Cognitive Status Telephone Interview-40 than those with non-severe cases and control individuals at 12 months (median [IQR]: severe, 22.50 [16.00-28.00]; non-severe, 30.00 [26.00-33.00]; control, 31.00 [26.00-33.00]). Severe COVID-19 was associated with an increased risk of early-onset cognitive decline (odds ratio [OR], 4.87; 95% CI, 3.30-7.20).

Comparison of Telephone Interview of Cognitive Status-40 (TICS-40) scores between severe COVID-19 survivors, non-severe COVID-19 survivors, and uninfected control individuals at 6 and 12 months was calculated using Wilcoxon test (Mann-Whitney U). The proportions of participants with different cognitive states at 6 and 12 months were calculated using the χ 2 test. Informant Questionnaire on Cognitive Impairment in the Elderly (IQCODE) scores ≥3.5 were considered indicative of cognitive impairment. A decrease of ≥3 points on the TICS-40 from baseline during follow-up was considered indicative of clinically significant cognitive impairment. H, Values ​​adjusted for age, sex, education, body mass index and each comorbidity using linear mixed effects models. Data normalization was performed using min-max normalization.

a Difference in mild cognitive impairment. 
b Difference in dementia.

Discussion

Postinfection cognitive outcomes following COVID-19 have been reported, but the long-term dynamic trajectory of cognitive changes in COVID-19 survivors remains unclear. Previous pandemics have provided evidence showing the adverse effects of severe respiratory diseases on cognitive functions.

Approximately 15% of patients infected with severe acute respiratory syndrome or Middle East respiratory syndrome showed long-term cognitive deficits, such as memory and attention problems. 22 With the increasing number of patients surviving COVID-19, the cognitive sequelae of this disease have attracted much attention.

Recent studies found that COVID-19 was associated with an increased risk of being diagnosed with dementia within 6 months of infection. Consistent with this, we found that approximately 3.3% of COVID-19 survivors had dementia and 9.1% had MCI at 12 months after discharge; In particular, the incidences of dementia and MCI were 15.00% and 26.15% in individuals with severe cases, respectively.

The incidence of dementia or mild cognitive impairment was not different between individuals with nonsevere cases and uninfected control individuals. These findings suggest that COVID-19, especially severe COVID-19, may be associated with long-term cognitive impairment.